Musashi-Mizonokuchi Station has one side platform for ascending traffic (for Kawasaki), and one island platform for descending traffic (for Tachikawa). Platform 3 is used for services originating at this station. The station building was rebuilt as an elevated station in 1998.

Musashi-Mizonokuchi Station opened as a station on the Nambu Railway on March 9, 1927. The Nambu Railway was nationalized on April 1, 1944 becoming part of the Japanese Government Railway (JGR) system, which became the Japan National Railways (JNR) from 1946. Freight services were discontinued on March 1, 1976. Along with privatization and division of JNR, JR East started operating the station on April 1, 1987.

In fiscal 2013, the station was used by an average of 81,503 passengers daily (boarding passengers only), making it the 53rd-busiest station operated by JR East.[1] The daily passenger figures (boarding passengers only) in previous years are as shown below.